Severe Bone Destruction Research Articles

Circadian rhythm disruption aggravates alveolar bone loss in rat apical periodontitis.

Circadian rhythm disruption (CRD) affects the expression levels of a range of biological clock genes, such as brain and muscle ARNT-Like-1 (BMAL1), which is considered to be an important factor in triggering or exacerbating inflammatory response. However, the underlying effect of CRD on the pathogenesis of apical periodontitis, a common oral inflammatory disease, currently remains unknown. Exploring the effects and pathogenic mechanisms of CRD on apical periodontitis will be beneficial in providing new ideas for the prevention and treatment of apical periodontitis. The cross-sectional study was conducted among patients with apical periodontitis visiting to hospital. Rat models combining CRD and apical periodontitis were constructed, and the destruction of periapical alveolar bone was assessed by Micro-CT, H&E, and TRAP staining assay. Rat periapical alveolar bone tissues were collected for RT-qPCR and immunohistochemistry to further detect the expression of periapical biological clock genes. A model of apical periodontitis was constructed using Bmal1-/- and WT rats to further verify the key role played by Bmal1. Finally, rats raised in CRD environment were intraperitoneally injected with melatonin to restore the circadian rhythm, and the periapical alveolar bone repair was observed by Masson's staining and staining of osteogenic markers (ALP, RUNX2). A close association between CRD and acute exacerbation of chronic apical periodontitis (CAP) in patients was first found in an epidemiological survey. By constructing animal models of CRD and apical periodontitis, it was found that CRD could aggravate the inflammatory stress of apical periodontitis and even drive the acute exacerbation of CAP. Further investigations suggested that the expression of crucial clock genes, especially Bmal1, were significantly disrupted in the periapical tissue of apical periodontitis. In addition, the periapical tissue from Bmal1 knockout rat displayed stronger inflammatory response and more severe alveolar bone destruction in apical periodontitis. Restoring circadian rhythm by melatonin supplementation could effectively alleviate both the inflammatory response and alveolar bone loss in apical periodontitis. CRD is a novel trigger in aggravating the inflammatory response and alveolar bone loss of apical periodontitis. Melatonin is expected to be used in the dental clinic as an important adjunctive therapy strategy for the healing of periapical tissue in apical periodontitis.

Eldecalcitol alleviates diabetic periodontitis by regulating macrophage efferocytosis and polarization via SOCE machinery.

Diabetes exacerbates the occurrence and severity of periodontitis, the pathogenesis of diabetic periodontitis (DPD) is influenced by the delayed resolution of inflammation. Eldecalcitol (ED-71) has shown promise in preventing bone loss in DPD. We herein aimed to investigate the role of ED-71 in the inflammatory regression phase of DPD and elucidate the underlying mechanisms. Type-2 diabetes was induced by streptozotocin injection in Wistar rats, and to explore the in vivo effect of ED-71 on macrophage efferocytosis, periodontitis was induced by ligation combined with lipopolysaccharide. Alveolar bone destruction was assessed using micro-computed tomography, hematoxylin-eosin, immunohistochemistry, and tartrate-resistant acid phosphatase staining. Immunofluorescence staining and flow cytometry detected neutrophils, apoptotic cells, and macrophage polarization in periodontal tissue. Additionally, flow cytometry, real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to examine macrophage efferocytosis and changes in store-operated calcium entry (SOCE). We found that rats with diabetes exhibited more severe alveolar bone destruction and increased neutrophil aggregates in periodontal tissue. Following the ED-71 administration, alveolar bone loss significantly decreased, and the immune microenvironment of periodontal tissue tended to suppress inflammation. Macrophages stimulated with high glucose experienced disruption of SOCE machinery, leading to the inhibition of efferocytosis in vitro. ED-71 demonstrated the ability to restore macrophage efferocytosis by correcting SOCE, and preventing sustained inflammatory damage to periodontal tissue. In conclusion, diabetes impairs macrophage efferocytosis and M2 polarization in periodontitis rats, resulting in the delayed resolution of inflammation. ED-71 could attenuate alveolar bone loss by mitigating macrophage via SOCE machinery in DPD.

VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN

Osteosarcoma (OS) is a highly aggressive malignant tumor with a high rate of disability and mortality rates, and dysregulated autophagy is a crucial factor in cancer. However, the molecular mechanisms that regulate autophagy in OS remain unclear. This study aimed to explore key molecules that affect autophagy in OS and their regulatory mechanisms. We found that fatty acid synthase (FASN) was significantly increased in activated autophagy models of OS and promoted OS proliferation in an autophagy-dependent manner, as detected by LC3 double-labeled fluorescence confocal microscopy, western blotting, transmission electron microscopy (TEM), and cell functional experiments. Furthermore, co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), ubiquitination modification, molecular docking, and protein truncation methods were used to identify FASN-interacting proteins and analyze their effects on OS. Valosin-containing protein (VCP) enhanced the FASN stability by recruiting ubiquitin specific peptidase-2 (USP2) to remove the K48-linked ubiquitin chains from FASN; domain 2 of VCP and the amino acid sequence () of USP2 were critical for their interactions. Gain- and loss-of-function experiments showed that the inhibition of FASN or USP2 attenuated the stimulatory effect of VCP overexpression on autophagy and the malignant phenotypes of OS cells in vitro and in vivo. Notably, micro-CT indicated that VCP induced severe bone destruction in nude mice, which was abrogated by FASN or USP2 downregulation. In summary, VCP recruits USP2 to stabilize FASN by deubiquitylation, thereby activating autophagy and promoting OS progression. The identification of the VCP/USP2/FASN axis, which mediates autophagy regulation, provides important insights into the underlying mechanisms of OS and offers potential diagnostic and therapeutic strategies for patients with OS.

RANKL-mediated osteoclast formation is required for bone loss in a murine model of Staphylococcus aureus osteomyelitis

Staphylococcus aureus osteomyelitis leads to extensive bone destruction. Osteoclasts are bone resorbing cells that are often increased in bone infected with S. aureus. The cytokine RANKL is essential for osteoclast formation under physiological conditions but in vitro evidence suggests that inflammatory cytokines may by-pass the requirement for RANKL. The goal of this study was to determine whether RANKL-dependent osteoclast formation is essential for the bone loss that occurs in a murine model of S. aureus osteomyelitis. To this end, humanized-RANKL mice were infected by direct inoculation of S. aureus into a unicortical defect in the femur. Mice were treated with vehicle or denosumab, a human monoclonal antibody that inhibits RANKL, both before and during a 14-day infection period. The severe cortical bone destruction caused by infection was completely prevented by denosumab administration even though the bacterial burden in the femur was not affected. Osteoclasts were abundant near the inoculation site in vehicle-treated mice but absent in denosumab-treated mice. In situ hybridization demonstrated that S. aureus infection potently stimulated RANKL expression in bone marrow stromal cells. The extensive reactive bone formation that occurs in this osteomyelitis model was also reduced by denosumab administration. Lastly, there was a notable lack of osteoblasts near the infection site suggesting that the normal coupling of bone formation to bone resorption was disrupted by S. aureus infection. These results demonstrate that RANKL-mediated osteoclast formation is required for the bone loss that occurs in S. aureus infection and suggest that disruption of the coupling of bone formation to bone resorption may also contribute to bone loss in this condition.

Nonsurgical Minimally Invasive Endodontic Treatment of Large Periapical Lesions: A Report of Three Cases

Introduction Periapical lesions develop as a result of microorganisms from necrotic pulp tissue or retained foreign bodies in the periapical tissue, leading to acute or chronic inflammation. It has been proven that the majority of inflammatory periapical lesions can be effectively treated using nonsurgical endodontic management. However, the selection between surgical and nonsurgical endodontic treatment for managing large periapical lesions remains a controversial issue. This report aims to reveal the effectiveness of nonsurgical, minimally invasive endodontic treatment for large periapical lesions in conjunction with lesion decompression and aspiration. Case Presentation This article presents three cases with large periapical lesions related to severe bone destruction with different causes that were managed with nonsurgical endodontic treatment, involving multiple visits for intracanal medication with calcium hydroxide. In all three cases, the long-term clinical assessments and CBCT scans consistently showed complete healing. The follow-up period ranged from 24 to 48 months. Conclusion The successful results demonstrated the efficacy of nonsurgical endodontic management, which is a minimally invasive approach when addressing large inflammatory periapical lesions with diverse causes.

COMBINATION OF REGENERATIVE THERAPY AND FREE GINGIVAL GRAFT IN STAGE IV PERIODONTITIS: CASE REPORT

Introduction: Periodontal regenerative therapy can be used to repair damaged periodontal tissues caused by periodontitis. The combination of regenerative periodontal surgery and FGG (Free Gingival Graft) is expected to accelerate the regeneration of periodontal tissue. Case : A 37-year-old woman came with complaints of loose lower front teeth, frequent bleeding and pain when eating and drinking. The complaint was felt since 1 year ago. Clinical examination obtained an average pocket depth of 6 mm and an average second degree of tooth mobility. On radiographic examination found bone damage horizontally. Case Management: The patient received root planing scaling and occlusion adjustment, followed by dental periodontal surgery 42,41,31,32. Stage II surgery for recession closure therapy with FGG was carried out three months after stage 1 surgery was performed. Discussion: Regenerative periodontal surgery is performed to produce new periodontal tissue growth and restore connective tissue attachment to the teeth. Free Gingival Graft is performed to increase gingival keratinization and improve patient esthetics. Conclusion and Suggestions: The combination of regenerative periodontal surgery and FGG for the treatment of periodontitis cases involving severe bone destruction gives good results of periodontal tissue healing by alveolar bone healing and regeneration and quite good aesthetics.

L-cysteine contributes to destructive activities of odontogenic cysts/tumor.

Odontogenic cysts/tumor can cause severe bone destruction, which affects maxillofacial function and aesthetics. Meanwhile, metabolic reprogramming is an important hallmark of diseases. Changes in metabolic flow affect all aspects of disease, especially bone-related diseases. At present, the researches on pathogenesis of odontogenic cysts/tumor are mainly focused on the level of gene regulation, but the effects of metabolic alterations on odontogenic cysts/tumor have still underexplored. Imaging analysis was used to evaluate the lesion size of different odontogenic lesions. Tartrate resistant acid phosphatase (TRAP) and immunohistochemistry (IHC) assays were utilized to detect the differences in bone destruction activity in odontogenic cysts and tumors. Furthermore, metabolomics and weighted gene co-expression network analysis (WGCNA) were conducted for the metabolomic features and key metabolite screening, respectively. The effect of ferroptosis inhibition on bone destruction was confirmed by IHC, immunofluorescence, and malondialdehyde colorimetric assay. The bone destruction activity of ameloblastoma (AM) was the strongest and the weakest in odontogenic cysts (OC). High-throughput targeted metabolomics was used to map the metabolomic profiles of OC, odontogenic keratocyst (OKC) and AM. WGCNA and differential analysis identified L-cysteine in OKC and AM. Cystathionine γ-lyase (CTH) was further screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The functions of L-cysteine were further validated. Finally, we confirmed that CTH affected destructive activities by regulating the sensitivity of epithelial cells to ferroptosis. High-throughput targeted metabolomics performed on diseased tissue confirmed the unique alteration of metabolic profiles in OKC and AM. CTH and its metabolite L-cysteine are the key factors regulating destructive activities.

Sclerotherapy for Aggressive Vertebral Hemangioma with Severe Bone Destruction: A 5-Year Analysis.

Sclerotherapy for Aggressive Vertebral Hemangioma with Severe Bone Destruction: A 5-Year Analysis.

Periodontitis promotes the progression of diabetes mellitus by enhancing autophagy

ObjectiveThis study aims to identify the periodontitis factor that activates excessive autophagy in pancreatic β cells, resulting in organic lesions of pancreatic islet tissues and diminished insulin secretion, thereby accelerating the progression of diabetes mellitus (DM). MethodsSprague-Dawley (SD) rats were induced with periodontitis (PD), type 2 diabetes mellitus (T2DM), or the combination of T2DM and PD (DP) through a high-sugar/high-fat diet and ligation of the tooth neck with silk thread. Alveolar bone resorption was assessed using Micro-CT, blood glucose levels were measured with a blood glucose meter, pancreatic tissue pathology was examined through HE staining, and the expression of autophagy-related proteins Beclin1 and LC3II/LC3I was analyzed using Western blotting. ResultsMicro-CT results revealed more pronounced alveolar bone resorption and root bifurcation exposure in the PD and DP groups compared to the control group, with the DP group exhibiting the most severe condition. HE staining demonstrated the formation of periodontal pockets, severe alveolar bone destruction, and abnormal pancreatic islet tissue morphology in the PD and DP groups. The serum levels of IL-6, TNF-α, and IL-1β increased sequentially in the control, DM, PD, and DP groups (P < 0.05). Relative expressions of GCK and GLUT-2 mRNA decreased in the PD group compared to the control group (P > 0.05), while the mRNA expressions in the DP and DM groups increased (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Western blot results indicated increased expression levels of autophagy proteins Beclin1 and LC3II/LC3I in the DM and DP groups compared to the control group (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). ConclusionThe findings demonstrate that periodontal inflammatory factors may promote the enhancement of pancreatic cell autophagy in diabetic rats.

Inhibition of Protein Disulfide Isomerase Attenuates Osteoclast Differentiation and Function via the Readjustment of Cellular Redox State in Postmenopausal Osteoporosis.

Due to the accumulation of reactive oxygen species (ROS) and heightened activity of osteoclasts, postmenopausal osteoporosis could cause severe pathological bone destruction. Protein disulfide isomerase (PDI), an endoplasmic prototypic thiol isomerase, plays a central role in affecting cellular redox state. To test whether suppression of PDI could inhibit osteoclastogenesis through cellular redox regulation, bioinformatics network analysis was performed on the causative genes, followed by biological validation on the osteoclastogenesis in vitro and ovariectomy (OVX) mice model in vivo. The analysis identified PDI as one of gene targets for postmenopausal osteoporosis, which was positively expressed during osteoclastogenesis. Therefore, PDI expression inhibitor and chaperone activity inhibitor were used to verify the effects of PDI inhibitors on osteoclastogenesis. Results demonstrated that PDI inhibitors could reduce osteoclast number and inhibit resorption function via suppression on osteoclast marker genes. The mechanisms behind the scenes were the PDI inhibitors-caused intracellular ROS reduction via enhancement of the antioxidant system. Micro-CT and histological results indicated PDI inhibitors could effectively alleviate or even prevent bone loss in OVX mice. In conclusion, our findings unveiled the suppressive effects of PDI inhibitors on osteoclastogenesis by reducing intracellular ROS, providing new therapeutic options for postmenopausal osteoporosis.

Echinococcus granulosus promotes bone resorption by increasing osteoclasts differentiation

Osseous cystic echinococcosis (CE) is a rare disease caused by Echinococcus granulosus, which is characterized by high morbidity, disability, and mortality. However, it is severely neglected due to its mainly regional epidemic. The development of osseous CE is usually accompanied by severe bone erosion and destruction at the site of infection; however, there is a gap in research on the mechanism of this phenomenon. The current treatment for this disease is single-sided, ineffective, and has a high rate of disability and recurrence. Our study investigated the mechanism of bone destruction caused by osseous CE and provided a theoretical basis for basic research and innovative ideas for treating clinical disease. A co-culture system of osteoclast progenitor cells and protoscoleces (PSCs) was established to test the effects of PSCs on osteoclast differentiation. We also created two disease models of spinal and femoral CE, with the highest incidence of osseous CE. We verified the effect of E. granulosus on osteoclasts at the infection site in vivo. The stimulatory effect of E. granulosus on osteoclast formation was confirmed by in vivo and in vitro experiments. This study elucidates the elementary mechanism of bone destruction in osseous CE and fills a gap in the field of basic osseous CE research, which is conducive to treating the disease.

Oral Manifestation of Papillon-Lefevre in Two Siblings

Background: Papillon-Lefèvre Syndrome (PLS) is a very rare genetic disorder (autosomal recessive) that usually affects infants between the ages of one and five years. PLS is characterized by palmar-plantar hyperkeratosis and premature loss of primary and permanent teeth with extensive, severe, and rapid destruction of the alveolar bone, leading to the premature loss of both teeth. Objective: To report on the management of PLS patients. Case: A 9-year-old girl and a 2.5-year-old boy from Nganjukto General Hospital, Pediatric Dentistry Division, RSGM Airlangga University with the main complaints of upper left tooth pain, rocking, difficulty eating, erythematous hyperkeratosis hands and feet, periodontal inflammation, mobility. bad teeth. Case Management: Nine-year-old girl: Teeth #26 and #46 could not be retained and extracted due to buccoversion and severe mobility. Periodontal supportive therapy was periodontal debridement, scaling and root planing and oral hygiene counseling with 0.20% chlorhexidine gluconate. Two-and-a-half-year-old boy: Too young, he is observed every 3 months. It is recommended to take vitamin B complex in appropriate doses and fruit juice as an additional supplement. Conclusion: Intensive periodontal treatment and administration of antibiotics only delays the progression of periodontal disease and cannot be used to prevent primary and permanent teeth. Extensive and repeated prosthodontic treatment is required to provide functional teeth to children during their period of jaw growth.

Clinical features of infectious spondylitis in patients with COVID-19

Objective. To analyze the clinical features of the course of infectious spondylitis in patients with COVID-19.Material and Methods. A continuous retrospective study was performed with the analysis of medical records of 52 patients with infectious spondylitis who were treated in 2021–2022. The patients were divided into two groups: the study group (n = 24) – with a history of a new coronavirus infection; and the control group (n = 28) – without coronavirus infection.Results. The features of infectious spondylitis in patients with COVID-19 are the predominance of facultative anaerobic gram-negative flora in the focus of infection, a higher frequency of multilevel lesions, a tendency to increase the number of negative results of surgical treatment, and a chronic protracted course. At the same time, the course of infectious spondylitis associated with COVID-19 is accompanied by less destructive changes in the affected segment leading to a violation of the supporting function of the spine. Nevertheless, there is a statistically significant increase in the period of relief of the inflammatory process in the spine in these patients: 18.04 ± 3.84 weeks in the study group and 10.08 ± 2.34 weeks in the control group (Uemp &lt; 240; p = 0.001).Conclusion. The secondary infectious lesion of the spine against the background of a new coronavirus infection is caused by gram-negative pathogens in the vast majority of cases, proceeds without severe bone destruction, with a tendency to a chronic protracted course. Surgical treatment of COVID-associated spondylitis is associated with a higher risk of postoperative complications.

Relative comparison of chronic kidney disease-mineral and bone disorder rat models.

Objective: The aim of this study is to establish a suitable animal model of chronic kidney disease-mineral and bone disorder (CKD-MBD) by comparing CKD-MBD rat models induced by 5/6 Nx, AN, and UUO, accompanied by a low-calcium and high-phosphorus diet. Methods: Sprague‒Dawley rats were randomly divided into four groups: control group, 5/6 nephrectomy (5/6 Nx) group, Adriamycin nephropathy (AN) group, and unilateral ureteral obstruction (UUO) group. Serum biochemical indices were measured to evaluate renal function, mineral and bone metabolism, the severity of CKD-MBD, and the status of bone transformation. Hematoxylin-eosin staining (HE) and Masson's trichrome (Masson) staining were used for histopathological analysis of the kidney. Goldner's trichrome (Goldner) and tartrate-resistant acid phosphatase (TRAP) staining were utilized to observe bone mineralization and osteoclasts in the femur, respectively. Micro-CT images were applied to study the structure of the femur. The expression levels of osterix and cathepsin K in the femur were measured by immunohistochemistry (IHC) to confirm the status of bone transformation. Results: The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the 5/6 Nx and AN group rats were significantly higher than those in the control rats, and this change was accompanied by marked changes in the levels of calcium (Ca), phosphate (Pi), intact parathyroid hormone (i-PTH), fibroblast growth factor 23 (FGF23), osteocalcin (OC), and cross-linked C-telopeptide of type 1 collagen (CTX-1); UUO group rats exhibited slight and inconsistent variations in the levels of Scr, BUN, Ca, Pi, i-PTH, FGF23, OC, and CTX-1 in serum. Histopathological analysis of the kidney showed that the UUO group rats suffered serious fibrosis and 5/6 Nx group rats exhibited severe focal calcification. Histopathological analysis of the femur showed that the AN group rats had minimal bone mineralization and that the 5/6 Nx group rats had overactive osteoclasts. Micro-CT revealed that the AN model had the most severe bone destruction and that the 5/6 Nx model had the least severe bone loss among the three models. The expression of cathepsin K in the femur was significantly increased in all models, while the expression of osterix in the femur was only significantly increased in the 5/6 Nx model. Conclusion: 5/6 Nx, AN, and UUO accompanied by a low-calcium and high-phosphorus diet successfully induced CKD-MBD in rats. The 5/6 NX model presented the progression of high-turnover bone disease, with consistency between biochemical indices in serum and histomorphometric analysis of the femur, and the AN and UUO models developed a severe deterioration in bone quantity and severe bone resorption; however, the changes in biochemical indices were subtle in the UUO model, and liver injury was obvious in the AN model.

Higher degree of keratinization correlated with severe bone destruction in acquired Cholesteatoma

Background Acquired cholesteatoma is characterized by hyper-keratinized squamous epithelium and bone destruction. However, direct evidence for hyper-keratinized epidermis promoting bone destruction is lacking. Aims/Objectives To determine whether higher degree of keratinization correlated with severe bone destruction and further offer direct evidence for keratinocyte-inducing osteoclastogenesis. Materials and Methods Histological changes and clinical relevance were analyzed in human-acquired cholesteatoma. Animal models were established by implanting autologous epidermis with different degrees of keratinization. The severity of bone resorption and the number of osteoclasts were compared in different keratinized groups. An in vitro coculture system was developed to mimic the progress of keratinocyte-inducing osteoclastogenesis. Results The matrix of cholesteatoma was composed of a thicker stratum corneum than normal skin. The stratum corneum thickness and the expression of Keratin 10 positively correlated to the severity of bone destruction. Animal models revealed that the bone destruction induced by a higher keratinized epidermis was more severe. Osteoclasts were detected in bone erosion areas, and the number of osteoclasts increased with the keratinization degrees of the graft. In vitro studies showed that keratinocytes directly promoted monocytes differentiating into osteoclasts. Conclusions and significance In acquired cholesteatoma, the degree of keratinization correlated with disease severity, and keratinocytes directly promote osteoclastogenesis.

Application of the Locking Compression Pediatric Hip Plate™ in children with proximal femoral tumors

BackgroundPediatric proximal femoral tumors often present with accumulative and severe bone destruction and are often complicated by pathological fractures and malunion. Such tumors are treated clinically by lesion scraping and graft reconstruction with autologous iliac bone alone or in combination with artificial bone. This study aimed to determine the efficacy of the Locking Compression Pediatric Hip Plate™ in treating pediatric proximal femoral tumors.MethodsFrom 2012–2017, the Locking Compression Pediatric Hip Plate™ was applied for internal fixation in 28 children in the Department of Pediatric Surgery. The complications were pathological fractures in 19 patients and multiple lesions in 5 patients. Tumors were removed by tumor curettage and reconstruction with autogenous iliac bone or artificial bone graft. The Locking Compression Pediatric Hip Plate™ was then applied. Postoperative pathological examination confirmed the diagnosis.ResultsThe cohort comprised 20 males and 8 females (mean age 7.8 ± 2.9 years). The mean follow-up duration was 26.1 ± 8.1 months (range 18–48 months). Post-treatment radiography showed that the lesions and local pathological fractures were healed in 3.2 ± 0.4 months (range 3–4 months), with no complications. Four patients continued to receive antineoplastic therapy postoperatively. Four patients experienced recurrence in situ, while another four developed distant metastases. The radiographic and joint function findings indicated that the affected limbs had excellent function. The mean Enneking score was 28.7 ± 1.0 points (range 27–30 points).ConclusionsInternal fixation with the Locking Compression Pediatric Hip Plate™ in children achieves good therapeutic effects. Moreover, the Locking Compression Pediatric Hip Plate™ resolves the shortcomings of external fixation by traditional plaster casts and internal fixation by Kirschner wires and elastic intramedullary screws.

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis.

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system’s and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures.

Mother's iliac bone graft for severe collapsed lumbar tuberculosis: A case report

AbstractEarly diagnosis of spinal tuberculosis in young children is difficult due to atypical clinical features. We report a case of lumbar tuberculosis with abscess of the psoas major muscle in a 4‐year‐old child. Spinal reconstruction was challenging due to the involvement of multiple vertebral levels. The child complained of lumbar and back pain. Preoperative magnetic resonance imaging (MRI) revealed bone destruction of the L1–L3 vertebral body and abscess formation of the psoas major muscle. The child underwent excision of the vertebral lesions and a fresh iliac bone graft from his mother through an anterior approach and posterior fixation with T12–L1 and L4–L5 pedicle screws. At the 15‐month follow‐up, the patient had good clinico‐radiologic outcomes with evidence of bony fusion. No functional impairment of lumbar movements was found through physical examination during the follow‐up period. The report highlights the diagnostic dilemma of early childhood spinal tuberculosis due to lesions seen both on radiology and during surgery and discusses challenges in management of the disease and the relevant literature. The mother's iliac bone graft we describe can be a viable option in very young children with severe vertebral bone destruction requiring reconstruction by surgical procedure.

Massive Juvenile Psammomatoid Ossifying Fibroma in the Mandible With a Complex Clinical Course: Case Report and Literature Review

The juvenile ossifying fibroma is a rare subset of the benign ossifying fibroma. These tumors have an aggressive behavior and often cause severe destruction of bone and surrounding tissue. JOF can be separated into the juvenile trabecular ossifying fibroma and juvenile psammomatoid ossifying fibroma. In this article, we present a case of an 18 year old male who presented with a rapidly growing massive tumor originating in the right mandible that caused severe local destruction. Due to the size of the tumor, the patient had impairment in many activities of daily living. Pre-operative management was further complicated due to the vascular nature of the tumor which resulted in spontaneous bleeding. The tumor was successfully resected and final pathology revealed a diagnosis of juvenile psammomatoid ossifying fibroma. In this article, we describe treatment of a debilitating mandibular tumor and provide recommendations for other clinicians who encounter similar cases. Additionally, the demographics and histopathological features of the juvenile ossifying fibroma and its subtypes are described.

Emerging nanotherapeutics alleviating rheumatoid arthritis by readjusting the seeds and soils.

Rheumatoid arthritis (RA) is a complicated autoimmune disease that results in severe joint inflammation, synovial hyperplasia, pannus formation, cartilage and bone destruction, and other RA-associated complications. Although the pathogenesis of RA remains unclear, increasing reports have shown that inflammation-relevant cells and the microenvironment of inflamed joints play a critical role in the formation and aggravation of RA. Recently, numerous nanotherapeutics have been engineered to overcome these intractable challenges by readjusting inflammation-related seeds (endothelial cells, macrophages, neutrophils, antigen-presenting cells, fibroblasts, osteoclasts, T cells, B cells, and chondrocytes) and inflamed soils (NO, cell-free DNA, hypoxia, ROS, and pro-inflammatory cytokines). In this review, we first present a detailed pathogenesis of RA, with an emphasis on the emerging advances in regulating seeds or remodeling soils for RA treatment. We then outline these intelligent therapeutics via synergistic seed-soil adjustment, particularly for spatiotemporally cascade-responsive or all-in-one integrational nanosystems. Finally, we briefly discuss the ongoing challenges and prospects for the clinical development and translation of seed soil-based therapies.